Maintenance and repair of skeletal muscle tissue is essential for survival of locomotor organisms. For example, muscle strains or tears can happen when a muscle is stretched beyond its limit or if there is a direct blow to a muscle, tearing the muscle fibers. Muscle injury frequently occurs near the point where the muscle joins the tough, fibrous connective tissue of the tendon. Muscle injuries are common and range from where only a few muscle fibers are stretched or torn, to more severe tears with muscle pain and tenderness, mild swelling, noticeable loss of strength and sometimes bruising, to muscle tears that rip the muscle into two separate pieces or cause the fleshy part of the muscle to break away from the tendon, resulting in complete loss of muscle function, considerable pain, swelling, tenderness and discoloration.
During aging, much of the muscle mass is lost. In addition, fiber-type changes occur and increased fat deposition in muscle occurs. Loss of mass and these other changes can have a significant impact on the ability of an individual to continue to perform certain daily activities, as well as participate in more strenuous activities, possible earlier in life.
In addition to regular maintenance and repair of muscle tissue that is associated with normal activities in most individuals, there are also significant diseases that affect the muscle tissue. The muscular dystrophies are a group of muscle diseases which have three features in common including hereditary; progressive; and cause a characteristic, selective pattern of weakness, in particular, progressive skeletal muscle weakness, defects in muscle proteins, and the death of muscle cells and tissue (e.g., see Emery A E (2002)).
Dystrophin-associated muscular dystrophies range from the severe Duchenne muscular dystrophy (DMD), which is the most common muscular dystrophy, to the milder Becker muscular dystrophy (BMD). Mapping and molecular genetic studies indicate that both are the result of mutations in the huge gene that encodes dystrophin. Duchenne muscular dystrophy eventually affects all voluntary muscles, as well as heart and breathing muscles. Survival is rare beyond the early 30 s, and death typically occurs from respiratory failure (suffocation) or heart disorders.
Satellite cells, which lie juxtaposed to the myofiber and underneath the basal lamina, are a source of new myonuclei required for skeletal muscle growth, repair and regeneration (see for example Mauro, 1961; Schultz and McCormick, 1994). In uninjured skeletal muscle, the majority of these cells are mitotically quiescent, exhibit a high nuclear to cytoplasmic volume and do not express members of the MyoD family of transcription factors (Cornelison and Wold, 1997; Schultz et al., 1978). Once activated, these cells rapidly increase their cytoplasmic volume, egress from the basal lamina and proliferate prior to their fusion into existing, damaged myofibers or with each other to form new myofibers (see for example Hawke and Garry, 2001; and Smith et al., 1994). Most satellite cells divide only once or twice prior to fusion and a subpopulation of satellite cells fail to fuse and fail to incorporate DNA label over 14 days, suggesting they comprise a quiescent “reserve” cell pool.
Accordingly, there remains a need for improved methods and compositions for the engraftment and/or repair of muscle tissue, including injured, aged and diseased muscle tissue.